Cardiopulmonary arrest remains one of the leading causes of death and disability in the U.S.A. The chances of survival following cardiac arrest are poor, despite fast emergency responses and better techniques of defibrillation. Cardiac arrest with its consequent disruption of blood flow sets in motion a cascade of cellular derangements that result in brain damage, which results from a number of factors, such as free radical formation, release of excitatory amino acids, mitochondrial dysfunction and synaptic dysfunction. Our main hypothesis is that synaptic dysfunction may play a key role in delayed neuronal cell death, and the protein kinase C exerts either positive/negative effects during the post-resuscitative period. The GOAL of proposed research is to define the mechanisms of synaptic dysfunction after cardiac arrest (CA) in the hippocampus. Since this is a broad area, we will emphasize the role of the protein kinase C signal transduction pathway in this pathology. Specific aims include: Specific Aim 1: To define the cellular locus of deltaPKC translocation in the CA1 region of the hippocampus after CA. Our hypothesis is that delta PKC translocates to both pre- and post-synaptic terminals of the CA1 hippocampus and that this triggers synaptic derangements after CA. A second hypothesis is that delta PKC translocation occurs in all three major cell types in the CA1 sub-region of the hippocampus following CA. Specific Aim 2: To define the intracellular locus of the delta PKC translocation in the CA1 sub-region of the hippocampus after CA. This aim will define the intracellular locus of delta PKC translocation following CA. Specific Aim 3: To define the delta PKC effect on synaptic physiology after CA. Under this aim, we will tackle one of the specific sites that we hypothesize is involved in CA induced damage, the synaptic terminal. Our hypothesis is that the delta PKC isozyme alters synaptic activity in such a way that it promotes synaptic dysfunction after CA.